DESCRIPTION (Adapted from applicant's abstract and specific aims): Apoptosis is a process that is widespread in nature and leads to non-necrotic cell removal during tissue remodeling. It involves a number of active cell processes including characteristic DNA fragmentation, morphologic alterations and surface changes that can be recognized by phagocytic cell, especially macrophages, leading to engulfment. Uptake and removal of apoptotic cells has been suggested to be involved in resolution of inflammation: the engulfment occurs prior to inflammatory cell lysis and is postulated not to lead to the normal pro-inflammatory sequelae of macrophage phagocytosis. Three main areas will be investigated: 1) The utilization by macrophages of different receptors for apoptotic cells will be examined in vitro and in pulmonary inflammation, as well as the outcome of inflammatory lesions in which such recognition and removal is inhibited. 2) The selective inability of macrophages to respond to uptake of apoptotic cells by elaboration of cytokines and other mediators of inflammation will be examined, testing the hypothesis that TGFb production actively inhibits the generation of other mediators and manifestations of macrophage activation. 3) The mechanisms by which the phospholipid membrane asymmetry is lost and PS is expressed during apoptosis will be explored.